Immunological imprinting of humoral immunity to SARS-CoV-2 in children

Alexander C. Dowell, Tara Lancaster, Rachel Bruton, Georgina Ireland, Christopher Bentley, Panagiota Sylla, Jianmin Zuo, Sam Scott, Azar Jadir, Jusnara Begum, Thomas Roberts, Christine Stephens, Shabana Ditta, Rebecca Shepherdson, Annabel A. Powell, Andrew J. Brent, Bernadette Brent, Frances Baawuah, Ifeanyichukwu Okike, Joanne BeckmannShazaad Ahmad, Felicity Aiano, Joanna Garstang, Mary E. Ramsay, Rafaq Azad, Dagmar Waiblinger, Brian Willett, John Wright, Shamez N. Ladhani*, Paul Moss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Original languageEnglish
Article number3845
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
The authors would like to express their gratitude to the children who took part in the Born in Bradford and sKIDs surveillance studies and also thank the schools, headteachers, staff and families of those involved. This study was funded by the UK Coronavirus Immunology Consortium (UK-CIC) and the National Core Studies (NCS) programme (P.M. and J.W.). B.W. was also funded in part by the MRC (MC UU 1201412). Figure 6 was created with BioRender.com.

Publisher Copyright:
© 2023, The Author(s).

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